It is now generally recognized that trace metals play an important role in mammalian nutriture and metabolism. Nonetheless, until relatively recently, it was assumed that the availability of dietary zinc was not a major concern for human populations. However, multiple studies conducted throughout the world, including Western populations, have indicated that marginal levels of zinc deprivation may in fact exist in human populations and that zinc deficiency may occur as a result of either inadequate zinc in the diet, or as a result of either inadequate zinc in the diet, or as a result of multiple conditioning factors, including pregnancy. Previous studies in rodents have suggested that short periods of zinc deprivation were significantly teratogenic. However, relatively mild cases of zinc deprivation, unlike those studied in rodents, are more relevant to human problems. A major concern in this regard is related to pregnant women. How can we best determine the optimal level of zinc nutriture, especially in regard to its relationship to fetal development? Moreover, if zinc deficiency has detrimental influences in humans, are any of these influences reversible if identified early in pregnancy? To investigate these problems, over the past two years of our three year program we have induced a marginal state of zinc deficiency in the pregnant non-human primate, Macaca mulatta, and have maintained a state of zinc deprivation throughout gestation and lactation. The results of these observations suggest that a marginally zinc deficient zinc diet, even when begun after conception, has marked influences on maternal and newborn health. These influences include nutritional status, anthropometric parameters, immunologic function, and behavior of newborn animals. In the continuing phase of this grant we hope to focus more directly on teratogenic influences of long term marginal zinc deprivation, begun 1 year prior to pregnancy, as well as on the possible reversibility of these effects. As such, we hope to define the role of zinc repletion of nutritionally at risk pregnancies. We will also continue our attention on the effects of long-term marginal zinc deprivation on offspring and will focus primarily on growth and development, immunohematologic function and behavioral development with specific attention to potential development disabilities.